Johns Hopkins University has had an ACTU since its inception in 1986. The Unit is administratively within the Division of Infectious Diseases as a component of the Johns Hopkins HIV Care Program, but it is configured to make maximum use of relevant institutional resources with investigators from multiple departments and divisions including Pharmacology, Neurology, Ophthalmology, Gynecology, Pathology and Internal Medicine. The Hopkins ACTU has provided leadership to the ACTG scientific agenda and has provided HIV clinical trials to Baltimore, a city that ranks ninth among metropolitan areas in AIDS rates. The performance record for the last grant cycle shows average enrollment, data performance and a rank of No. 3 in scientific contributions. Assets of this ACTU include leadership and scientific expertise in virology (B. Jackson), immunology (H. Lederman, T. Quinn, R. Bollinger), quality of life assessment (A. Wu), neurology (J. McArthur), pharmacology (C. Flexner), CMV retinitis (D. Jabs), and mycobacteriology (R. Chaisson). This unit has a subunit in the prison system, has developed an ACTG study of tuberculosis in Haiti and has high enrollment of injection drug users and African-Americans. This application proposes to continue a scientific portfolio that has depth and diversity to support the ACTG scientific agenda and a clinical trials program that includes good data performance and the enrollment of high priority participants. All current investigators will continue in their present roles as will the three advanced technology laboratories. Three new investigators, Dr. R. Siliciano (latent reservoirs of HIV), Dr. Richard Moore (HIV outcomes, cost and cost effectiveness), and Dr. David Thomas (hepatitis C co-infection) will be added. Preference will be given to protocols that reflect emphasis areas of the Hopkins ACTU, especially pharmacology, neurology, immunology, mycobacteriology, hepatitis C, long-term outcomes (quality of life and cost analyses) and simplified ART regimens (to better serve the patients). There will be emphasis on enhanced enrollment with a new peer recruiter and a new subunit to increase the catchment area.